Current research focuses primarily on the use of human mitochondrial DNA in forensic applications and disease diagnostics. In addition, we are developing Standard Reference Materials (SRMs) for improved human mitochondrial DNA amplification and sequencing (SRM 2392 and 2392-I), for detection of low-frequency heteroplasmic mutations (SRM 2394), and for accurate detection of the correct number of triplet repeats in Fragile X patients and their relatives (SRM 2399). Our overall goal is to detect DNA damage and the chemical alterations of DNA bases following exposures to chemical (e.g., environmental toxicants) and physical (e.g., ionizing radiation) agents. In individuals with specific diseases, actual DNA base pair sequence changes have been observed in both mitochondrial and nuclear DNA. When all of the cells have the same altered genotype, these changes or mutations are fairly easy to determine with PCR and sequencing. However, little research has been conducted to examine the mitochondrial DNA damage from environmental exposures or the specific mutations (actual base pair changes) that such exposures can cause. The need for this information comes from the knowledge that such mutations can lead to many diseases.

We are currently examining the low-frequency heteroplasmic single nucleotide polymorphisms (SNPs) and mutations found in mitochondrial DNA (especially those associated with diseases) and allele frequencies of SNPs in nuclear DNA of pooled samples from populations, the latter in collaboration with the National Human Genome Institute and Johns Hopkins University . The aim of this latter research project is to enable the screening of populations with and without specific diseases and to detect associated SNPs that may have a causal relationship with the disease. Diseases that we have examined include:  Mitochondrial Encephalomyopathy, Lactic Acidosis and Stoke-like Episodes (MELAS), Chronic Progressive External Ophthalmoplegia (CPEO), and Leber's Hereditary Optic Neuropathy (LHON).

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